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Chapter 26 : Autophagy: a Fundamental Cytoplasmic Sanitation Process Operational in All Cell Types Including Macrophages

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Abstract:

Autophagic degradation is a cell-autonomous mechanism for direct elimination of intracellular microbes, but also plays a broader role in innate and adaptive immunity and in general cytoplasmic homeostasis. The process of autophagy plays many functions, including feeding the cells under starvation conditions or upon withdrawal of growth factors. Autophagy plays both housekeeping and immune functions in macrophages and dendritic cells. The phagophore is enlarged by the addition of a new membrane that is of undefined origin but is suspected to come from the endoplasmic reticulum or a combination of sources including Golgi and endosomes. Most cells undergo baseline autophagy, removing protein aggregates and spuriously damaged mitochondria or other organelles, or adjusting the cellular biomass. The classical physiological inducers of autophagy are amino acid starvation or absence of growth factors. Recent studies examining effects on the redistribution of a sole integral membrane Atg protein, Atg9, have implicated ULK1 as the putative mammalian Atg1 ortholog. A classical physiological inducer of autophagy is amino acid starvation, in particular, withdrawal of leucine. In mammalian cells, the role of autophagy has been linked to immunological signals. In mice and humans it is under the control of cytokines and agonists regulating innate and adaptive immunity, such as interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin 13 (IL-13), and CD40L-CD40.

Citation: Deretic V. 2009. Autophagy: a Fundamental Cytoplasmic Sanitation Process Operational in All Cell Types Including Macrophages, p 419-425. In Russell D, Gordon S (ed), Phagocyte-Pathogen Interactions. ASM Press, Washington, DC. doi: 10.1128/9781555816650.ch26

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Tumor Necrosis Factor alpha
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Plasma Membrane
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Endoplasmic Reticulum
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Figures

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FIGURE 1

Execution stages of the autophagic pathway. See text for explanations. Reproduced with permission from .

Citation: Deretic V. 2009. Autophagy: a Fundamental Cytoplasmic Sanitation Process Operational in All Cell Types Including Macrophages, p 419-425. In Russell D, Gordon S (ed), Phagocyte-Pathogen Interactions. ASM Press, Washington, DC. doi: 10.1128/9781555816650.ch26
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Image of FIGURE 2
FIGURE 2

Core signaling pathways regulating autophagy. Light gray boxes, agonists of autophagy (positive regulators); dark gray boxes, antagonists of autophagy (negative regulators). See text for description and explanations.

Citation: Deretic V. 2009. Autophagy: a Fundamental Cytoplasmic Sanitation Process Operational in All Cell Types Including Macrophages, p 419-425. In Russell D, Gordon S (ed), Phagocyte-Pathogen Interactions. ASM Press, Washington, DC. doi: 10.1128/9781555816650.ch26
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Image of FIGURE 3
FIGURE 3

Immunologically relevant inputs (dotted boxes) and outputs (solid boxes) of autophagy. See text for details and references. Adapted from .

Citation: Deretic V. 2009. Autophagy: a Fundamental Cytoplasmic Sanitation Process Operational in All Cell Types Including Macrophages, p 419-425. In Russell D, Gordon S (ed), Phagocyte-Pathogen Interactions. ASM Press, Washington, DC. doi: 10.1128/9781555816650.ch26
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